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New test shows if DCIS breast cancer will spread

13 December, 2013

“New test for breast cancer that could spare thousands needless treatment,” the Daily Mail reports. Researchers have identified a molecule – integrin αvβ6 – that appears to be associated with the development of invasive breast cancer.

The research investigated an early type of breast cancer called ductal carcinoma in situ (DCIS). DCIS means there are abnormal cancer cells in the breast ducts, but the cancer has not yet spread.

In up to half of DCIS cases the cancerous cells stay where they are. But in the other half of cases the cells spread into other tissues of the breast, and can then spread to other parts of the body.

The difficulty is in accurately predicting which half a woman falls into. As a precaution, all women with DCIS are usually offered treatment, typically a combination of surgery and radiotherapy. This means up to 2,400 women a year in the UK may receive unnecessary treatment.

The new research suggests that DCIS cells with higher levels of integrin αvβ6 were more likely to progress to invasive breast cancer than those with lower levels.

The implication is that testing integrin αvβ6 levels would identify women with “low risk” DCIS and spare them unnecessary treatment.

However, the results suggest the test had a small but important false negative rate; that is it gave an “all clear” result in some cases that progressed to invasive cancer.

This highlights the important fact that it is unlikely a single molecule will be able to predict disease progression in all women.

The results are certainly promising, but the headlines seem to have jumped the gun in welcoming a clinically useful test in the near future.

Where did the story come from?

The study was published in the peer-reviewed science journal: Clinical Cancer Research.

Generally the media reported the study accurately but many of the news sources implied that this test would quickly be introduced into standard clinical practice. This doesn’t seem likely.

For example the Daily Mail reported the test could be available on the NHS in five years. This appears optimistic given the research authors’ own conservative conclusions.

What kind of research was this?

This was a laboratory study using human and laboratory grown cells. It was looking to find biological signals explaining why a certain type of early breast cancer known as ductal carcinoma in situ (DCIS) develops into life threatening invasive breast cancer in some women but stays as a non aggressive, non life threatening form in others.

DCIS means there are abnormal cancer cells in the breast ducts, but the cancer has not spread out into the breast tissue. If not treated, up to half of people with DCIS will go on to develop potentially life threatening invasive breast cancer where the cancer has spread into the breast tissue with potential for spread to the lymph nodes and other tissues and organs of the body. The other half will have tumours that remain confined to the ducts and so aren’t threatening to health.

The problem is that scientists and medical professionals can’t tell in advance whether DCIS will progress to invasive cancer or will be the non-aggressive kind that remains confined to the ducts. So currently all women with DCIS are assumed to be at risk of invasive breast cancer and are offered the same treatment as a precaution. Treatment options are relatively radical and include surgery to remove breast tissue and or radiotherapy; both of which can cause physical and emotional distress.

So,up to 50% of women with DCIS have significant cancer treatment for a cancer that may not have developed into the life-threatening form, simply as a precaution.

What did the research involve?

This research analysed cancer cells from the tumours of 532 women with DCIS, as well as looking at records of how their disease developed (or didn’t develop). They wanted to work out what biological factors might predict whether DCIS would develop into invasive breast cancer.

Any biological factors identified would have the potential to be used to identify women at high or low risk of disease and potentially spare some women unnecessary treatment.

The research focused on a biological signalling molecule called integrin αvβ6 and involved a large range of biological tests, counter tests and confirmatory tests, to investigate the role of this molecule in the growth and invasion of tumour cells in the laboratory.

What were the basic results?

Integrin αvβ6 was not found in normal breast cells. Significant amounts were found in between 52% and 69% of DCISs that did not go on to become invasive. Much higher levels, between 87% and 96%, were found in DCIS cases that did go on to become invasive.

Investigating the biology of the tumour cells and linking them to records of disease progression showed the levels of integrin αvβ6 in the DCIS cells was significantly associated with progression to invasive breast cancer and its recurrence later in life.

This was backed up by results in the laboratory showing tumour cells with higher levels of integrin αvβ6 promoted tumour cell invasion and growth.

The investigations also found a way to block the tumour promoting effect of tumour cells expressing integrin αvβ6.

How did the researchers interpret the results?

The researchers concluded that altered tumour cells in DCIS predict disease progression and recurrence and demonstrate that cells expressing more integrin αvβ6 promote tumour growth in the laboratory. They suggest the expression of integrin αvβ6 may be used to stratify people with DCIS into those at more and less risk of progressing to invasive breast cancer.

They also highlight that further research should be done on their other finding that showed a way to block tumour progression, which is perhaps equally important as the other findings but received less prominence in the write up and in the media.

Considering the implications of their research as a whole, they report: “this may represent a key stage in the evolution of breast cancer that could be used in a predictive and prognostic setting, allowing more tailored management of women with DCIS, and may offer opportunities for therapeutic intervention.”

Conclusion

This research used tumour cells from 532 women to show ductal carcinoma in situ (DCIS) cells with raised levels of integrin αvβ6 were linked to the progression and recurrence of invasive breast cancer later in life.

In addition, laboratory investigations also confirmed integrin αvβ6 had tumour-promoting properties and suggested a biological mechanism to inhibit breast cancer growth linked to this molecule.

Currently breast tissue samples of women with DCIS are routinely taken to assess the biology of the early stage tumour. The implication of this research is that levels of integrin αvβ6 could be measured at this stage and used to predict which tumours are likely to progress to invasive breast cancer and which aren’t, potentially avoiding unnecessary surgical and radiological treatment in some women.

The study is certainly a big step forward in understanding DCIS, but a usable test that could reliably sort women into those that will get breast cancer and those that won’t still appears some way off as the test is far from perfect.

For example, elevated integrin αvβ6 levels were still found in between 52% and 69% of DCIS cases that did not go on to become invasive breast cancer.

It was higher in those that did go on to develop invasive breast cancer (between 87% and 96%) but was not 100%.

This is problematic because any test based on results like this would mean at least 4-13% of the women with DCIS would be given an all clear result, but would later go on to develop the invasive disease and may not receive treatment early enough to be effective.

The potential consequences of getting it wrong are so serious that any test would need to be extremely accurate. Ideally you would want a test with a false negative rate as close to 0% as possible. This could also be achieved by using multiple different tests together.

Nonetheless, looking at integrin αvβ6 levels in combination with other biological markers (yet to be discovered) or other risk factors (yet to be discovered) may improve the accuracy of any potential test to a point where it is medically useful in the future. Also understanding exactly how integrin αvβ6 drives tumour growth could potentially lead to new treatments.

The researchers themselves don’t herald a new test quite yet, and cautiously report that: “further studies are needed to establish whether integrin αvβ6 could be used in the clinical setting to stratify patient care”.

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